U.S. Pat. No. 5,382,600 discloses (substituted) 3,3-diphenylpropylamines useful for treating urinary incontinence. In particular, it discloses 2-[(1R)-3-(diisopropylamino)-1-phenylpropyl)-4-methylphenol, also known as N,N-diisopropyl-3-(2-hydroxy-5-methylphenyl)-3-phenylpropylamine, with the generic name of tolterodine, as being useful to treat urinary incontinence. Tolterodine is the compound of Example 22 of U.S. Pat. No. 5,382,600.
It is preferred that tolterodine is prepared by the processes of International Publication WO98/29402 (U.S. Pat. No. 5,922,914).
H Postlind et al, Drug Metabolism and Disposition, 26(4): 289-293 (1998) discloses that tolterodine is a muscarinic receptor antagonist. It is presently being sold in a number of different countries for treatment of urinary incontinence under the name Detrol®, marketed by Pharmacia. When tolterodine is used to treat urinary incontinence it is administered perorally as a tablet. The major, active metabolite of tolterodine is the 5-hydroxymethyl derivative of tolterodine.
U.S. Pat. No. 5,559,269 and H Postlind et al, Drug Metabolism and Disposition, 26(4): 289-293 (1998) disclose hydroxytolterodine. U.S. Pat. No. 5,559,269 discloses this compound as being useful to treat urinary incontinence. Pharmacol. Toxicol., 81: 169-172 (1997) discloses that hydroxytolterodine has antimuscarinic activity.
The international patent application WO98/43942 discloses therapeutically active diarylpropylamines, which have favorable anticholinergic properties, and which can be used for the treatment of disorders related to urinary incontinence.
WO 02/34245 discloses the use of tolterodine for treating asthma, COPD, and allergic rhinitis.
The currently marketed administration form of tolterodine is film-coated tablets containing 1 mg or 2 mg of tolterodine L-tartrate, or extended release capsules containing 2 mg or 4 mg of tolterodine L-tartrate for release in the gastrointestinal tract. Consumers constantly require alternative delivery forms with favorable efficacy and/or which simplify the treatment, thus improving their quality of life.
Atropine methonitrate and ipratropium are quaternary ammonium derivatives of atropine. Ipratropium bromide is used by inhalation to produce bronchodilation. Ipratropium is 8-isopropylnoratropine methobromide and is disclosed in U.S. Pat. No. 3,505,337.
Yono M et al, European Journal of Pharmacology (1999) 368:223-230, is concerned with the pharmacological effects of tolterodine, an antimuscarinic drug, in isolated human urinary bladder smooth muscle.
Ruffmann R et al, The Journal of International Medical Research (1998) 16:317-330, reviews use of flavoxate hydrochloride or alternative compounds, such as terodiline hydrochloride and emepronium bromide, in the treatment of urge incontinence.
Stewart B H et al, The Journal of Urology (1976) 115:558-559 discloses therapy of mild to moderate stress urinary incontinence with a combination of phenylpropanolamine hydrochloride, chlorpheniramine maleate, and isopropamide iodide in a sustained release capsule.
WO 95/10269 and WO 95/10270 disclose the use of R- and S-terodiline, respectively, as drugs for treating conditions related to the compounds' activities as anticholinergic agents.
Despite the above advances in the art, it is desirable to develop novel pharmaceutical compounds that further improve the quality of life for a large number of individuals.